PREGNANCIES FOLLOWING HIGH-DOSE CYCLOPHOSPHAMIDE WITH OR WITHOUT HIGH-DOSE BUSULFAN OR TOTAL-BODY IRRADIATION AND BONE-MARROW TRANSPLANTATION

Patients successfully treated with a marrow transplant often have conc erns about fertility and pregnancy. This study was performed to determ ine pregnancy outcome among patients who had received high-dose chemot herapy alone or with total-body irradiation (TBI) and marrow transplan tation for aplastic anemia or hematologic malignancy. Records of 1,326 postpubertal and 196 prepubertal patients currently more than 12 year s of age after marrow transplant in Seattle from August 1971 to Januar y 1992 were reviewed to determine the patients with normal gonadal fun ction and pregnancies. Among 708 postpubertal women, 110 recovered nor mal ovarian function and 32 became pregnant. In addition, nine formerl y prepubertal girls with normal gonadal function became pregnant. Amon g 618 postpubertal men, 157 recovered testicular function and partners of 33 became pregnant. An additional two formerly prepubertal men had partners who became pregnant. Forty-one female patients and partners of 35 male patients had 146 pregnancies after transplant. All 76 patie nts responded to a questionnaire requesting pregnancy history, outcome , infant birth weight, and congenital anomalies information for all cl inically recognized pregnancies. There were 115 live births among 146 (79%) pregnancies. Spontaneous abortion terminated four of 56 (7%) pre gnancies for 28 female cyclophosphamide (CY) recipients and six of 16 (37%) pregnancies for 13 TBI recipients (P = .02). Partners of 28 male CY recipients had four of 62 (6.4%) pregnancies terminate with sponta neous abortion, but there were no spontaneous abortions among eight pr egnancies of five TBI recipients' partners. Preterm delivery occurred for eight of 44 (18%) and five of eight (63%) live births for 24 CY an d eight TBI female recipients (P = .01). This 25% incidence among all female patient pregnancies is higher than the expected incidence of 8% to 10% (P = .0001). The 13 preterm deliveries resulted in 10 low birt h weight ([LBW] 1.8 to 2.24 kg) and three very low birth weight ([VLBW ] less than or equal to 1.36 kg) infants, for an overall incidence of 25%, which is higher than the expected incidence of 6.5% for the gener al population (P = .0001). Twelve of the 13 premature infants survive. Congenital anomalies were seen among two of 52 (3.8%) live-born infan ts of female and six of 63 (9.5%) live-born infants of male patients, which is not different from the 13% of single congenital anomalies rep orted for the general population, These data demonstrate that clinical ly recognized pregnancies among women who have received a marrow trans plant incorporating TBI are likely to be accompanied by an increased r isk of spontaneous abortion. Pregnancies among all women who received a marrow transplant are likely to be accompanied by preterm labor and delivery of LBW or VLBW babies who do not seem to be at an increased r isk of congenital anomalies. However, determination of possible advers e effects of parental exposure to high-dose alkylating agents with or without TBI on children born posttransplant requires longer, additiona l follow-up. (C) 1996 by The American Society of Hematology.